Pancreatic ductal adenocarcinoma (PDAC) is an intractable clinical problem, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. Currently, the standard diagnostic course includes CT or MRI scans which do not have optimal sensitivity and specificity for accurately diagnosing and determining resectability status. The long-term objectives of this project are to develop an imaging agent that can sensitively and accurately detect pancreatic cancer. To that end, we are developing a targeted imaging agent to the newly identified pancreatic cancer cell surface biomarker plectin-1. Plectin-1 is specifically expressed in pancreatic cancer and not in benign inflamed conditions. It is upregulated during carcinogenesis and expressed at high levels in the advanced premetastatic PanIN III lesions. Moreover, a SPECT/CT plectin-1 targeted imaging agent has been developed and validated in numerous stringent mouse models. Experiments will be performed to optimize the imaging agent's molecular configuration and imaging modality. Outcomes will lead to a lead imaging product that will be advanced to phase II for commercial product development and clinical study. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to develop new imaging approaches for the detection of pancreatic cancer, determine cancer resectability status and monitor response to chemotherapy. Alternative uses include early diagnostic screening in individuals with high-risk for the development of pancreatic cancer. We will do this by chemically synthesizing imaging agents and testing them in mouse models of pancreatic cancer. We will also test whether PET or SPECT imaging has the best characteristics for imaging pancreatic cancer.